An analysis of the possibility for health implications of joint actions and interactions between food additives

The possibility that structurally unrelated food additives could show eithe r joint actions or interactions has been assessed based on their potential to share common sites and mechanisms of action or common pathways of elimin ation. All food additives approved in the European Union and allocated nume rical acceptable daily intake values were studied, initially based on the r eports by the FAO-WHO Joint Expert Committee for Food Additives. Target org ans were identified based on the effects reported at doses above the no-obs erved-adverse-effect level (NOAEL) in animal and human studies. The descrip tions of the pathological and other changes reported were used to assess wh ether different additives, sharing the same target organ, would produce a c ommon toxic effect. In all but a very few cases, the possibility of joint a ctions or interactions could be excluded on scientific grounds. The excepti ons were on the liver (curcumin, thiabendazole, propyl gallate, and BHT), t he kidney (diphenyl, o-phenylphenol, and ferrocyanide salts), the blood (az orubine and propyl gallate), and the thyroid (erythosine, thiabendazole, an d nitrate). Toxicokinetic interactions were considered unlikely because of the low dosages involved, the diverse nature of the routes of metabolism an d elimination, and the fact that enzyme induction or inhibition would have influenced selection of the NOAEL. Many of those additives which could not be excluded from showing joint actions or interactions would have low intak es; in some cases they were alternatives for the same application, thereby further lowering the combined intake. In consequence, joint actions or inte ractions between additives do not represent a significant health concern. ( C) 2000 International Life Sciences Institute.